counter to the needs of a proliferating cell. Some
glucose must be diverted to macromolecular
precursors such as acetyl-CoA for fatty acids,
glycolytic intermediates for nonessential amino
acids, and ribose for nucleotides. This may explain
at least part of the selective advantage provided by
the Warburg effect, a hypothesis supported by
recent 13C–nuclear magnetic resonance spectroscopy
measurements showing that glioblastoma cells
in culture convert as much as 90% of glucose and
60% of glutamine they acquire into lactate or
alanine (16). Although most of this lactate and
alanine is excreted from the cell as waste, one “byproduct”
of their generation is a robust production
of NADPH (Fig. 3). In addition to providing nitrogen
for nonessential amino acids through transamination
reactions, the catabolism of glutamine into
lactate produces NADPH via the activity of